The cost-utility of dabigatran etexilate compared with warfarin in treatment and extended anticoagulation of acute VTE in the UK

Summary

The relative efficacy and safety of dabigatran etexilate and warfarin have been evaluated in two head-to-head, phase III, treatment of acute venous thromboembolism (VTE) trials, and one extended prophylaxis trial, in patients with high risk of recurrent VTE. Dabigatran etexilate demonstrated similar efficacy to warfarin, and was associated with a reduced risk of major or clinically relevant bleeds. Based on results of these trials, and real-life disease prognosis following discontinuation of anticoagulation treatment, we evaluated the cost-utility of dabigatran etexilate compared with warfarin in six months anticoagulation, and in extended, up to 24 months anticoagulation, in patients with acute VTE, acute deep-vein thrombosis (DVT) or acute, symptomatic, pulmonary embolism (PE). Costs were analysed from the perspective of the National Health Services (NHS) and Public Social Services (PSS) in England and Wales. Outcomes were quantified in quality-adjusted life years (QALY). The estimated incremental, lifetime cost/QALY gain following acute, symptomatic VTE (DVT or PE) was £1,252/QALY when dabigatran etexilate or warfarin were administered for up to six months treatment. In treatment of acute, symptomatic PE and in DVT respective ratios were £1,767/QALY and £1,075/QALY. In extended, up to 24 months anticoagulation, dabigatran etexilate projected costs/QALY of £8,242/QALY, when compared with warfarin. Results obtained herein were robust across a number of sensitivity analyses and suggest dabigatran etexilate to be a cost-effective alternative to current standard of care when evaluated in six months treatment and in extended anticoagulation following acute VTE (DVT and/or PE).

Keywords

Venous thrombosis - anticoagulation - treatment - cost-effectiveness - economics

• References

• 1 Torbicki A, Perrier A, Konstantinides S. et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008; 29: 2276-2315.
• 2 Schulman S, Kearon C, Kakkar AK. et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med 2013; 368: 709-718.
• 3 Prins MH, Lensing AW, Bauersachs R. et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J 2013; 11: 21.
• 4 Halperin JL, Hankey GJ, Wojdyla DM. et al. Efficacy and Safety of Rivaroxaban Compared With Warfarin Among Elderly Patients With Nonvalvular Atrial Fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Circulation 2014; 130: 138-146.
• 5 Connolly SJ, Ezekowitz MD, Yusuf S. el al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
• 6 Hokusai-VTE Investigators Büller HR, Décousus H. et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013; 369: 1406-1415.
• 7 Agnelli G, Buller HR, Cohen A. et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369: 799-808.
• 8 Agnelli G, Buller HR, Cohen A. et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013; 368: 699-708.
• 9 Schulman S, Kearon C, Kakkar AK. et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361: 2342-2352.
• 10 Schulman S, Kakkar AK, Goldhaber SZ. et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 2014; 129: 764-772.
• 11 Coleman CI, Limone BL, Bookhart BK. et al. Cost-effectiveness analysis of extended duration anticoagulation with rivaroxaban to prevent recurrent venous thromboembolism. Thromb Res 2014; 133: 743-749.
• 12 Seaman CD, Smith KJ, Ragni MV. Cost-effectiveness of rivaroxaban versus warfarin anticoagulation for the prevention of recurrent venous thromboembolism: a U. S. perspective. Thromb Res 2013; 132: 647-645.
• 13 National Institute for Health and Clinical Excellence.. Guide to the methods of technology appraisal. 2013 Available online at: http://publications.nice.org.uk/guide-to-THe-methods-of-technology-appraisal-2013-pmg9 accessed July 7, 2014.
• 14 Schulman S, Eriksson H, Goldhaber SZ. et al. Treatment of Acute Pulmonary Embolism With Dabigatran or Warfarin: A Pooled Analysis of Data From RECOVER™ and RECOVER™ II,. ESC Congress, Barcelona; Spain: 30 August–3 September 2014
• 15 Prandoni P, Noventa F, Ghirarduzzi A. et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007; 92: 199-205.
• 16 EINSTEIN–PE Investigators Büller HR, Prins MH. el al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012; 366: 1287-1297.
• 17 EINSTEIN Investigators Bauersachs R, Berkowitz SD. et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010; 363: 2499-2510.
• 18 Lenert LA, Soetikno RM. Automated computer interviews to elicit utilities: potential applications in the treatment of deep venous thrombosis. J Am Med Inform Assoc 1997; 4: 49-56.
• 19 Prandoni P, Villalta S, Bagatella P. et al. The clinical course of deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients. Haematologica 1997; 82: 423-428.
• 20 Pengo V, Lensing A, Prins M. et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004; 350: 2257-2264.
• 21 Rosand J, Eckman MH, Knudsen KA. et al. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004; 164: 880-884.
• 22 Dolan P. Modeling valuations for EuroQol health states. Med Care 1997; 35: 1095-1108.
• 23 Marchetti M, Pistorio A, Barone M. et al. Low-molecular-weight heparin versus warfarin for secondary prophylaxis of venous thromboembolism: a cost-effectiveness analysis. Am J Med 2001; 111: 130-139.
• 24 NICE technology appraisals guidance [TA327]; Dabigatran etexilate for the treatment and secondary prevention of deep vein thrombosis and/or pulmonary embolism. December 2014 available at http://www.nice.org.uk/guidance ta327 accessed January 28, 2014.
• 25 Wolowacz SE, Roskell NS, Maciver F. et al. Economic analysis of dabigatran etexilate for the prevention of venous thromboembolism following total knee and hip replacement surgery. Clin Ther 2009; 31: 1-19.
• 26 Faria R, Spackman E, Burch J. et al. Dabigatran for the prevention of stroke and systemic embolism in atrial fibrillation: A NICE single technology appraisal. Pharmacoeconomics 2013; 31: 551-562.
• 27 Kansal AR, Sorensen SV, Gani R. et al. Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation. Heart 2012; 98: 573-578.
• 28 Evidence Review Group Report commissioned by the NIHR HTA Programme on behalf of NICE. Rivaroxaban for the treatment of pulmonary embolism and the prevention of recurrent venous thromboembolism. Available at: http://www.nice.org.uk/guidance/ta261/resources/evidence-review-group-report2 Accessed July 15, 2014
• 29 NICE technology appraisals [TA261]; Rivaroxaban for the treatment of deep vein thrombosis and prevention of recurrent deep vein thrombosis and pulmonary embolism,. July 2012 available at http://www.nice.org.uk/guidance ta261; accessed October 8, 2014.
• 30 NICE technology appraisals [TA287]; Rivaroxaban for treating pulmonary embolism and preventing recurrent venous thromboembolism. June 2013 available at: http://www.nice.org.uk/guidance/ta287 accessed October 8, 2014.